More than twenty years ago the first gene was synthesized by means of traditional chemical methods. These traditional methods relied on the use of protecting reagents for those reaction groups in nucleosides and nucleotides which are sensitive to the condensing agents required to form the phosphodiester bounds. These sensitive groups include the amino groups of the bases, the 3′- and 5′-hydroxy groups of the deoxyribose, and the phosphate group itself. Additionally, these traditional methods of nucleic acid synthesis relied on supports and linker compounds as an anchor for the nascent nucleic acid strand.
In many applications, it is desirable to have the nucleic acid strand released from the linker support. This cleavage is usually accomplished at the linker through chemical treatment that leads to the removal of certain groups and the resultant release of the nucleic acid from the support. Thus various methods have been developed to bind the beginning of the nucleic acid strand to the solid support via a linker that is susceptible to cleavage by chemical treatment, as well as methods for the efficient release of undamaged nucleic acid strand from the anchor.
These traditional approaches, however, are cumbersome and time consuming in terms of resulting percentage yield of the desired product (e.g. DNA and/or RNA). What is needed, therefore, is a more efficient and versatile method for nucleic acid synthesis.